Enzyme from ‘killer bacteria’ could save seriously ill kidney patients

What if you could take a substance that allows a nasty bacterium to resist the human immune system and develop it into a drug to help people with completely different diseases? It sounds like a fairy tale for medical researchers. Yet this is precisely what is about to happen in Lund.

Lars Bjorck

Lars Björck hopes that the enzyme IdeS can be used to treat a number of autoimmune diseases.

The nasty bacterium is a streptococcus. It can sometimes be harmless; sometimes it causes sore throat and skin infections, but in the worst cases it causes very serious infections which can result in multiple organ failure. These infections can be fatal, which is the reason why the streptococcus is known as the ‘killer bacterium’.

In order to tackle human immune defences, the streptococcus uses a special substance, an enzyme called IdeS. IdeS disarms the antibodies that mark the bacterium. Read more under “How it works”.

“The enzyme is uniquely targeted against the antibodies, which is exactly what you want in a drug. A good drug should affect the target and nothing else,” explains Professor of Infection Medicine Lars Björck.

But would you really want to weaken part of the body’s crucial immune system? Yes, you would, in some cases:

“We have autoimmune diseases, which depend on the immune system starting to attack the body itself. We also have patients who need an organ transplant such as a kidney, but whose antibodies react against all possible transplants. In both these contexts, the ability to shut down the immune system could be used to the patient’s advantage”, says Lars Björck.

The latter possibility is soon to be tested, as the IdeS enzyme has been through the animal experiment stage and is in the process of being tested on humans. The first study has already been completed. It was a so-called phase 1 study, which involves determining whether an intended drug is safe and harmless. The study showed that IdeS splits antibodies even more effectively in humans than in laboratory animals, and does so without any side-effects.

The next study of IdeS is to cover patients who need a new kidney, but whose immune defences have already shown in laboratory tests to react against all potential transplants. These patients constitute 15 to 30 per cent of all seriously ill kidney patients. As they cannot receive transplants, they are currently referred for years of dialysis and often die prematurely.

“The idea is to inject IdeS in connection with the transplant in order to subdue the patient’s immune defences. If this works as predicted, the acute risk of organ rejection will disappear. The immune system will gradually return to its full strength, at which point we hope that the new kidney will have been accepted by the body”, says Lars Björck.

The clinical tests are being conducted in cooperation between Lars Björck’s research team and a small Lund company, Hansa Medical. Bo Håkansson, a well-known entrepreneur in Skåne, has supported the basic research for many years and in return has got ”first dibs” on its commercially viable results. Lars Björck, who has collaborated with both large companies and small ones such as Hansa Medical, thinks the difference is like night and day:

“Dealing with the big companies is awful! They have no scientific perseverance, they don’t give researchers the necessary freedom, and they are top-down, bureaucratic and non-creative organisations.

“I know of extremely few talented researchers who have voluntarily left academia to go to the pharmaceutical industry, even though the salaries are higher. Not being allowed to choose your own research project and research issues is a limitation of freedom which is off-putting for someone with a genuine scientific interest. I am not in the least surprised that the large pharmaceutical companies, in spite of their enormous financial resources, have a desperately hard time coming up with new concepts and drugs”, he says.

Lars Björck, his colleagues and Hansa Medical are also currently discussing other diseases that are unusual and hard to treat, which the IdeS enzyme might help to combat. These include neuromyelitis optica, an autoimmune disease which damages the vision and spinal cord, and SLE (lupus), a rheumatic disease which damages several different organs. If these also go well, further diseases may be taken into consideration. That would be a good sequel to the true story of the useful enzyme from the nasty streptococcus.

Text: Ingela Björck

Photo: Gunar Menander

How it works

When the streptococcus bacteria have infected a human being, they are usually discovered by specialised antibodies which attach themselves to the surface of the bacteria. The antibodies have a protruding part which functions as a ‘flag’ and signals to the white blood cells to come and kill the bacteria. The bacteria defend themselves, however, by allowing their enzyme to snip off the protruding ‘flag’, so that the white blood cells never find them.

The researchers’ ground-breaking discovery was made when they tested the bacterium’s enzyme on rabbits. They were amazed to find that the enzyme sabotaged the flags on all the IgG antibodies (an important part of our immune defences) in the rabbits’ blood.  Nevertheless, the rabbits were completely healthy, and their antibodies returned after a few days. Thus the enzyme has the ability to put the immune system out of action for a brief period of time, without damaging any other functions in the body.